Involvement of prolonged ras activation in thrombopoietin-induced megakaryocytic differentiation of a human factor-dependent hematopoietic cell line.

Molecular and Cellular Biology
I MatsumuraYuzuru Kanakura

Abstract

Thrombopoietin (TPO) is a hematopoietic growth factor that plays fundamental roles is both megakaryopoiesis and thrombopoiesis through binding to its receptor, c-mpl. Although TPO has been shown to activate various types of intracellular signaling molecules, such as the Janus family of protein tyrosine kinases, signal transducers and activators of transcription (STATs), and ras, the precise mechanisms underlying TPO-induced proliferation and differentiation remain unknown. In an effort to clarify the mechanisms of TPO-induced proliferation and differentiation, c-mpl was introduced into F-36P, a human interleukin-3 (IL-3)-dependent erythroleukemia cell line, and the effects of TPO on the c-mpl-transfected F-36P (F-36P-mpl) cells were investigated. F-36P-mpl cells were found to proliferate and differentiate at a high rate into mature megakaryocytes in response to TPO. Dominant-negative (dn) forms of STAT1, STAT3, STAT5, and ras were inducibly expressed in F-36P-mpl cells, and their effects on TPO-induced proliferation and megakaryocytic differentiation were analyzed. Among these dn molecules, both dn ras and dn STAT5 reduced TPO- or IL-3-induced proliferation of F-36P-mpl cells by approximately 30%, and only dn ras could inhibit ...Continue Reading

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Citations

Feb 27, 2001·Japanese Journal of Cancer Research : Gann·T SugimotoS Hattori
Oct 31, 2009·Journal of Thrombosis and Haemostasis : JTH·S SéverinA Mazharian
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Apr 23, 2002·Journal of Cellular Biochemistry·Ying ZhangKatya Ravid
Jul 4, 2002·International Journal of Hematology·Itaru Matsumura, Yuzuru Kanakura
Aug 30, 2003·The Journal of Biological Chemistry·Yoshihisa KataokaYuzuru Kanakura
Dec 31, 2002·Blood·Akira KawasakiYuzuru Kanakura
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